4-(2-pyrryl) thiazoles and 4-(2-pyrryl) selenazoles



Patented Sept. 13, 1949 4- (Z-PYRRYL) THIAZOLES AND 4- (2- PYRRYL)SELENAZOLES Edward B. Knott,.Frances M. Hamer, and Russell J. Rathbone,Harrow, WealdstoneEngland, as-

signors to Eastman Kodak Company, Y., a corporation of- New Jersey ter,N.

Roches- No Drawing. Application February '7', 1946, Serial No. 646,208.In Great Britain March 1, 1945 Claims.

This invention relates to 4-(2-pyrryl) thiazoles and. 4-(2-pyrryl)selenazoles, to a process for preparing the same, to quaternary saltsprepared from. the said' thiazoles and selenazoles, and to d yespreparedfrom said quaternary salts.

It is known that Z-methyl--(Z-thienyl) thiazole. can be prepared byhalogenating methyl 2-thi'enyl ketone and condensing the resultinghalogenomethyl 2-thienyl ketone with thioacetamide. We have now foundthat 2-substituted 4-(2-pyrryl) t h i a z o l e s and Z-substituted4-(2-pyrryl) selenazoles, which differs essentially from the known4-(2-thienyl) thiazoles, can be prepared by condensing a halogenated2-pyrry1 ketone with a thioamide or a selenoami'de which contains agroup (or a -d=NH group depending upon whether the thioamide Actuallyeither structure can be employed to represent the amides and the twoforms are probably in equilibrium with one another) It is, accordingly,an object of our invention to provide 2-substituted-4-QZ-pyrryl)thiazoles and 2-substituted 4 (Z-pyrryl) selenazoles and a process forpreparing the same. A further object is to provide quaternary saltsprepared from such thiazoles and selenazoles and to provide dyesprepared from such quaternary salts. Qther objects will become apparenthereinafter.

- In accordance with our invention, we prepare Z-Substitutedl-(Z-pyrryl)thiazoles and 2-substituted -4-(2py-rryl) selenazoles by condensing anamide selected from the group consisting of thioamides containing a sn-JJ=NH group and selenoamides containing a SeH =NH group, with a ketoneselected from the group wherein R, R1 and X have the values. givenabove, Q represents a member selected from the group consisting of asulfur atom and a selenium atom, and R2 represents a member selectedfrom the group consisting of an amino group, an alkylamino group, anaralkylamino, an arylamino group, an alkyl group, an aralkyl group, andan aryl group.

Examples of the thioamides and selenoam-idefi are: thioacetamide,selenoacetamide, thiourea, phenylthiourea, thiopropionamide,thiobenzamide, methylthiourea, benzylthiourea, thiophenylacetamide, etc.

Examples of the halogenated ketones are: 2 chloroacetyle-pyrrole,2z-bromoacetylpyrrole, 2- iodacetylpyrrole, 2-(cr-Ch0l01'0PIODlO1'1Y1)pyrrole, 2-(phenylchloroacetyl)- pyrrole, 2- (oz-chlorouphenylpropionyl) pyrrole, etc.

The condensation is advantageously effected in a solvent, e. g. analcohol, such as methyl, ethyl, isopropyl, n-propyl, isobutyl, n-butylalcohols, etc. Equimolecular proportions of the ketone and amide areadvantageously employed. The reaction takes place rapidly at elevatedtemperatures and may be accelerated by the addition of alkalies, e. g.alkali carbonates or bicarbonates (sodium or potassium carbonate orbicarbonate for example). a

The following examples will serve to illustrate further the manner ofpracticing our invention.

Example 1 ;'2-amino=4- (Z-pyrryl) thiazole...

s HC-CH El \E/ \N fhieurea (1.52 g.), 2=chloroacetylpyrrole Example2l--2-methyl-4-(2-pyrryl) thiazole HC CH HO Thioacetamide (1.5 g.),2-chloroacetylpyrrole (2.87 g.) and ethyl alcohol (1000.) were refluxedto form a solution, and anhydrous potassium carbonate (2 g.) was addedto the solution. The whole was then refluxed for 30 minutes, shaking sothat the color remained yellow. Upon dilution of the mixture with water,the above-formulated base precipitated as an oil which soon solidified.After 2 hours, it was collected and recrystallized from methanol. Itformed colorless glassy: aggregates melting at 94 to 95 C. It can alsobe purified by distillation (B. P. 171 C. at 18 mm. of Hg pressure) orby steam distillation. In a manner similar to that illustrated in theforegoing examples, 2 methyl 4 (2 pyrryl) selenazole can be preparedfrom seleoacetamide and 2-chl0roacetylpyrrole; 2-ethyl-4- (Z-pyrryl)thiazole can be prepared from thiopropionamide and2-chloroacetylpyrrole; 2-phenyl-4-(2-pyrryl) thiazole can be preparedfrom thiobenzamide and 2-chloroacetylpyrrole, etc.

. The halogenated 2-pyrryl ketones employed in practicing our inventioncan be prepared according to the method described by Blick, Faust,Gearien and Warznski, J. Am. Chem. Soc. 65, 2465 (1943) e. g.2-chloroacetylpyrrole can be formed from pyrrole and chloroacetonitrile,or the halogenated 2-pyrryl ketones can be prepared according to themethod described by Oddo and Machini, Gazz. chim. ital. (2) 42, 260(1912).

We have also found that the heterocyclic bases of our invention can beconverted to quaternary salts of the following general formula: III. /Q\

wherein R, R1, R2 and Q have the values given above, and R3 representsan alkyl or aralkyl group On cooling, the hydrohalide of 4 and Xrepresents an anion. Such quaternary salts are formed by heating thebases with an alkyl or aralkyl salt, e. g. methyLp-tolue'nesulfonate,ethyl-p-toluene'sulfonate, methyl benzenesulfonate, ethyl' iodide,n-propyl bromide, benzylchloride, dimethyl sulfate, diethyl sulfate,etc.

The following example will serve to illustrate further the preparationof such quaternary salts.

Example 3.-2-.methyZ-4- (Z-pyrryl) thiazole etho-p-toluenesulfonate 0gosoOoH, 2-methyl-4-(2-pyrryl)thiazole (3.3 g., 1 mol.) andethyl-p-toluenesulfonate (4.03 g., 1 mol.) were heated togetherin an oilbath at 1209C. for 2 hours. More ethyl-p-toluenesulfonate (4.03 gs 1mol.) was then added and heating at 120 CL was continued for a further 3hours. The resultant thick oil was lute diethyl ether.

In a similar manner, other alkyl salts, e. g.

those mentioned abov can be heated with the bases to give quaternarysalts, using a sealed tube where the alkyl salt is too volatile to beused in an open vessel. 1

The quaternary salts of the followin general formula:

IV. Q

Bil

wherein R, R1, R3, Q and X have the values given above can be condensedwith cyolammonium quaternary salts containing in the ozor 'y-position(i. e. one of the so-called reactive positions) a thioether group or aselenoether group, to give monomethine cyanine salts (or dyes). Th condensations are advantageously effected in the presence of a basiccondensing agent, e. g. a tertiary amine (triethylamine, triamylamine,N- methylpiperidine, dimethylaniline, etc.) or an alkali metal carbonate(sodium or potassium carbonate) illustrate further the preparation ofsuch cyam'ne salts which are represented by the following generalformula:

instance thiazole, 4-methylthiazole, -phenylthiazole, 4-(2-thienyl)thiazole, benzothiazole, 5- chlorobenzothiazole, a-naphthothiazole,fl-naphthothiazole, etc), a heterocyclic nucleus of the oxazole series(for instance 4-methyloxazole,

purified by washing with abso The following examples will serve to I H2-methy1-4- (2-pyrry1) thiazole etho-p-toluenesulfonate (3.63 g., 1mol.), 2-ethylthioquinoline etho-p-toluenesulfonate ('3;89 g., 1 mol.),triethylam-ine (2.75 00., 2 mol.) and ethyl alcohol cc.) were boiled andstirred together for 3 minutes-.. The hot. solution was poured into ahot solutionaof. potassium iodide (6.6 g., 4 mols.) in water (20cc). Atar precipitated and solidified on cooling. It was filteredofi, washedwith water and with diethyl ether, and then recrystallized from methylalcohol (60' cc.). After a second recrystallization from methyl alcohol,the reddish brown crystals of the above-formulated cyanine iodide-had ameltlngpoint of 227C. with decomposition Its: methyl alcoholic. solutionhad an absorption maximum at 4.79 mu. The cyanine iodide sensitized agelatino-silver-bromiodide photographic emulsion with a maximum at 535mu and a gelatino-silver-chloride photographic emulsion with a maximumat 520 mu.

Example 5..-[2-{'3-ethg l-4- (Z-pyrryl) thiazol'eH (Z-('3ethylbenzothiazolefl methinecycmi'ne iodide2:-methy:l4-(2-pyrryl)-2'-methylthiazole ethoe patoluenesul-fonate (3.63g., 1 mol.), 2-ethylthiobenzothiazoleetho-p-toluenesulfonate (3.96 g., 1mol.) triethylam-lne (2.75 ea, 2- mols.) and ethyl alcohol (20 cc.) wereboiled and stirred together for-3 minutes. The hot solution was pouredinto a hot solution of potassium iodide (6.6 g., 4 mols.) in water (20cc.) When cooled, the solid cyanine iodide formulated above was filteredoff, and washed with water and with diethyl ether. It was recrystallizedfrom methyl alcohol (150 cc.). The resulting dull yellow crystals meltedat 262 C. with decomposition. A methyl alcohol soluti'ouof the. crystalshad an absorption maximum at 4117: mu. The cyanine iodidesensitized aphoto'- graphic gelatino-silver-chloride emulsion with a at.4570-480 mu.ilmrarslmilar manner other of our new quaternary salts represented byFormula IV above can be condensed! with cyclarmmonium quaternary salt-scontaining a thi'oether or selenoether (e. g. methylthio; ethylthio,benzylthio, phenylthio, ethylseleno, :etc.) group in the ocor'y-position.

6 Ourneew'opuaternary' salts: are represented by Formula IV above camalsov he. condensed with; a trialkylorthoiomnate to. give symmetricaltrimethinecyanine salts, (:or dyes) The condom sations areadvantageously carried out. in the presence: of a basic. condensingagent,v e'.. g; pyridine, triethyrlamine; etc; The. following exam-.-ple will serve. inc-illustrate further'the preparation or thetrimethinecyaninea salts which are represented by: the following generalformula :1 v1; Q Q

R1.C./ \Q-R|. R y C=OHLCH*=CHC L as R; X

wherein R, R1,, R3,. Q; and'X representv the values given above.

Example 6 .-Bis-2'- [S-ethyt-el- (2-pyrryl') thz' azole]-trimethinecycminc iodide. s s

21 i I. H Z -methyll-IZ-pyrryD thiazole- (3228* g;, 2 mole) and ethylp-toluenesulfonate (4 g., 2 mols.)'= were heated together in an oil bathat fill- C. for S'hou-rs. The product was dissolved in hot pyrid ine (30cos), treated withethyl orthoformate (5 cc., 3 mols.), and the mixtureheated under reflux for one hour. The hot solution was poured intoa hotsolution of potassium iodide (6.7 g., 4 mols.) inwater 30cc); A purpletar-precipitated and it solidified upon grinding with cold water. It wasrecrystallized from methyl alcohol (20* 00.). The resulting blackcrystals melted at 199-202 C. with decomposition. Their methyl alcoholsolution had its absorption maximumat 555 mu. The cyaninesalt sensitizeda gelatinosilver-bromide photographic emulsion up to 640 mu with a flatmaximum between 570--and- 620- mu.

In a similar manner bis-2- 3-methyl-4-(2- pyrryl) thiazolel-trimethinecyanine iodide can be prepared from 2 methyl l-('2-pyrryll-thiazol'e metho-p-toluenesulfonate bis-2- E3-propyl-4- 62'-pyrryl) -thiazolel-trimethinecyanine iodide from 2 methyl-l-Q-pyrryl)thiazole propo-p-tollfenesulf'onate, etc.

Our new quaternary salts which are represented by Formula IV above canalso be condensed with diarylformamidines, e. g. diphenylformamidine,with an alkyl i'soformanilide or with an alkylisothioformanilid'e, e. g.methylisothioformanilide, to give fi-arylaminovinyl' derivatives ortrimethinecyanine salts. With equimolecular proportions of thequaternary salts and diphenylformamidine an alkylisoformanilide or analkylisothioformanilide, B-arylaminovinyl derivatives of the followinggeneral formula are obtained:

VII.

R? X wherein Q, R, R1, R3 and X have the values given above, and R5represents an aryl group. With a -arylaminovinyl derivative of FormulaVII, our new quaternary salts condense, in the presence of anacid-binding agent, e. g;, triethylamine or 7 piperidine, to give thetrimethinecyanine salt defined by Formula VI.

In the preparation of photographic emulsions containing our new dyes, itis only necessary to disperse the dyes in the emulsions. The methods ofincorporating dyes in emulsions are simple and well known to thoseskilled in the art. It is convenient to add the. dyes from solutions inappropriate solvents. Methanol has proven satisfactory as a solvent forour new dyes. Acetone may also be employed where the solubility of thedyes in methanol is lower than desired.

Sensitization by means of our new dyes is, of course, directed primarilyto the ordinarily employed gelatino silver halide developing outemulsions. The dyes or advantageously incorporated in the washed,finished emulsions and should, of course, be uniformly distributedthroughout the emulsions.

The concentration of our new dyes in the emulsion can vary widely, i. e.from about to about 100 mgs. per liter of flowable emulsion. Theconcentration of the dye will vary according to the type oflight-sensitive material in the emulsion and according to the effectsdesired. The suitable and most economical concentration for any givenemulsion will be apparent to those skilled in the art upon making theordinary tests and observations customarily used in the art of emulsionmaking.

To prepare a gelatino-silver-halide emulsion sensitized with one of ournew dyes, the following procedure is satisfactory: A quantity of the dyeis dissolved in methyl alcohol or other suitable solvent and a volume ofthis solution (which may be diluted with water) containing from 5 to 100mgs. of dye is slowly added to about 1000 cc. of agelatino-silver-halide emulsion, with stirring. Stirring is continueduntil the dye is uniformly distributed throughout the emulsion. Withmost of our new dyes, 10 to mgs. of dye per liter of emulsion sufficesto produce the maxi mum sensitizing effect with the ordinarygelatinosilver-bromide (including bromiodide) emulsions. With fine-grainemulsions, which includes most of the ordinarily employedgelatino-silver chloride emulsions, somewhat larger concentrations ofdye may be necessary to secure the optimum sensitizing effect.

The above statements are only illustrative and are not to be understoodas limiting our invention in any sense, as it will be apparent that ournew dyes can be incorporated by other methods in many of thephotographic silver halide emulsions customarily employed in the art.For instance, the dyes may be incorporated by bathing a plate or filmupon which an emulsion has been coated, in the solution of the dye, inan appropriate solvent. Bathing methods, however, are not to bepreferred ordinarily.

What we claim as our invention and desire to be secured by LettersPatent of the United States is:

1. A process for preparing a 4-(2-pyrryDazole comprising condensing anamide selected from the group consisting of amides represented by thefollowing general formula:

group consisting of a sulfur and a selenium atom, and R2 represents amember selected from the 2 from the group of wherein R represents a2-pyrryl group, R1 repre-- sents a member selected from the groupconsisting of a hydrogen atom, an alkyl group, an-

aralkyl group and an aryl group, and X'represents a halogen atomselected from the group consisting of a chlorine atom, a bromine atomand an iodine atom.

2. A process for preparing a 4-(2-pyrryl) thi-, azole comprisingcondensing a thioamide, selected from the groupof thioamides representedby the following general formula:

yC-Rg HN wherein R2 represents a member selected from the groupconsisting of an amino group, an alkylamino group, an 'aralkylaminogroup, an arylamino group, an alkyl group, an aralkyl group and an arylgroup, witha ketone selected from those represented by the followingeneral formula: Y r j 1 wherein R represents a 2-pyrry1 group, R1represents a member selected from the groupcone sisting of a hydrogenatom, an alkyl group, an aralkyl group and'an aryl group, and Xrepresents a halogen atom selected from the group consisting of achlorine atom, a bromine atom and an iodine atom.

3. A process for preparing a 4-(2-pyrryl) thiazole comprising condensinga thioamide selected thioamides represented by the following generalformula:

CItz HN wherein R2 represents a member selected from the groupconsisting of an amino group, an alkylamino group, an aralkylaminogroup, an aryl amino group, an alkyl group, an aralkyl group and an arylgroup, with a ketone selected from those represented by the followinggeneral formula: a RC 0-CH-Cl wherein R represents .a 2-pyrryl group andR1 represents a member selected from the group consisting of a hydrogenatom, an alkyl group, an aralkyl group and an aryl group. a a

4. A process for preparing 2-amino-4-(2- pyrryDthiazole comprisingcondensing thiourea with 2-chloracetylpyrrole. 1

5. A process for preparing 2-methyl 4-(2-' pyrryDthiazole comprisingcondensing thioacetamide with 2-chloroacetylpyrro1e.

6. A process for preparing 2-methyl-4-(2- pyrryDthiazole comprisingcondensing, in the presence of an alkali metal salt selected from thegroup consisting of alkali metal carbonates and alkali metalbicarbonates, thioacetamide with 2-chlorcacetylpyrrole.

7. The 4-(2-pyrryl) azoles which are represented by the followinggeneral formula:

wherein R. represents a Z-pyrryl group, R1 represents a member selectedfrom the group consisting of a hydrogen atom, an alkyl group, an aralkylgroup and an aryl group, R2 represents a member selected from the groupconsisting of an amino group, an alkylamino group, an aralkylaminogroup, an arylamino group, an alkyl group, an aralkyl group and an arylgroup, and Q represents a member selected from the group consisting of asulfur atom and a selenium atom.

8. The 4-(2-pyrryDthiazoles which are represented by the followinggeneral formula:

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,213,986 Kendall Sept. 10, 1940-2,304,112 Middleton Dec. 8, 1942 2,423,709 Knott July 8, 1947 OTHERREFERENCES Richters Organic Chemistry, vol. 3, pp. 12- 38.

Certificate of Correction Patent No. 2,481,674 September 13, 1949 EDWARDB. 'KNOTT ET AL.

It is hereby certified that errors appear in the printed specificationof the above numbered patent requiring correction as follows:

Column 2,1111544, for chloroacetyle-pyrrole read chloroacetyl-pyrrole;line 45, for iodacetylpyrrole read iodoacetylpyrrole; column 3, line 49,for seleoacetamide read selenoacetam'ide;

and that the'said Letters Patent should be read With these correctionstherein that the same may conform to the record of the case in thePatent Office.

Signed and sealed this 24th day of January, A. D. 1950.

THOMAS F. MURPHY,

Assistant Uommz'ssz'aner of Patents;

